**9. Extrapolating butterfly toxicology to humans**

The evaluation of the field effects may not be straightforward because of its indirect nature; however, our system for the internal exposure experiments likely reflects both the direct effects and some of the indirect field effects based on the use of the field-collected host-plant leaves for butterfly larvae. Because the larvae are highly resistant against the internal exposure to pure radioactive cesium (unpublished data), the high mortality and abnormality rates from the contaminated leaves can be largely attributed to the indirect field effects. It should be noted that what was measured in our experiments was the radioactivity concentration of radiocesium; however, other radioactive and nonradioactive materials were released from the Fukushima nuclear reactors, and these materials may have also contaminated the leaves. In this sense, *the radioactivity concentrations of radiocesium can be considered as an indicator of the degree of the pollution*. This is an important difference from the conventional dosimetric approach. To our knowledge, quantitative toxicological data that reflected some of the field effects were available only for butterflies. Thus, it is interesting to apply these data to humans to roughly grasp the collective effects of the Fukushima nuclear accident. Although there is no rigorous reason to believe that the butterfly data are applicable to humans, this attempt can be justified because of the lack of human-specific data and data from other organisms that reflect both the direct effects and indirect field effects.

ground radiation dose and/or the distance from the nuclear reactors and that state the biological effects in the field were reproduced dose-dependently in laboratory experiments are entirely valid. The main reason for this discrepancy is the exclusion of the field effects in the UNSCEAR assessment. In contrast, our experiments were constructed to reflect real-world phenomena, including the direct effects and indirect field effects. Furthermore, contrary to the UNSCEAR statement above, there were no major confounding factors in our study [9]

Moreover, the UNSCEAR statement completely ignores the process of logical judgment in terms of the cause of the Fukushima nuclear accident. The causality of the effects of the accident should be evaluated systematically according to logical postulates such as "the Postulates of Pollutant-Induced Biological Impacts" [45]. This includes six clauses that must be met to prove the causality of the pollutant(s) from a given source, i.e., spatial relationship, temporal relationship, direct exposure, phenotypic variability or spectrum, experimental reproduction of external exposure, and experimental reproduction of internal exposure [45]. The causality

The UNSCEAR 2017 Report [91] further commented on our paper in paragraph 134, in which

*134. Hiyama et al. [H9] provided further evidence to suggest that the high abnormality rates observed in the pale grass blue butterfly were induced by "anthropogenic radioactive mutagens." However, Otaki [O12] synthesized the results from several studies of the effects on the same species of butterfly following the FDNPS accident, and reported that ionizing radiation was unlikely to be the exclusive source of the* 

The above comments on our research are misleading; specifically, the last sentence wrongly implies that "the environmental disturbances observed" were caused by unknown confounding factors that were not related to the Fukushima nuclear accident. Rather, in Otaki [48], I mentioned the importance of the field effects from both radioactive and nonradioactive materials from the Fukushima Dai-ichi Nuclear Power Plant. In other words, "ionizing radiation" (i.e., the direct effects in the context of Otaki [48]) was not the exclusive source. It is entirely valid to say that the high abnormality and mortality rates observed in the butterfly were caused by the pollutants from the Fukushima nuclear accident. This UNSCEAR case indicates the low level of understanding regarding the field effects and the lack of fundamental logic among the researchers who contributed to the formulation of these paragraphs in the UNSCEAR 2017 Report [93]. On the other hand, these misleading comments may be understandable, considering that we presented the topic of indirect field effects only briefly in our previous papers. There is an urgent need for more precise explanations and experimental

The evaluation of the field effects may not be straightforward because of its indirect nature; however, our system for the internal exposure experiments likely reflects both the direct effects and some of the indirect field effects based on the use of the field-collected host-plant

because it consisted of controlled laboratory experiments.

60 New Trends in Nuclear Science

should not be judged solely from a dosimetric standpoint.

**9. Extrapolating butterfly toxicology to humans**

*environmental disturbances observed.*

validation of this issue.

H9 and O12 refer to Hiyama et al. [14] and Otaki [48], respectively.

The basic experimental strategy was to collect the polluted food (i.e., plants) from Fukushima and feed the plant samples to butterfly larvae from Okinawa, which was the least polluted locality in Japan. When non-contaminated leaves were fed to larvae, normal individuals emerged. However, when polluted leaves were fed to larvae, morphologically abnormal adults emerged, and the mortality of larvae and pupae was high. The abnormality rate and the mortality rate were then obtained for each polluted diet. Because the radioactivity concentration of radiocesium species (134Cs plus 137Cs) in foods (Bq kg−<sup>1</sup> diet) and the amount of food that each larva ate (g) was available, a dose-response curve was obtained [12].

*The half abnormality dose* (equivalent to median toxic dose, TD50; called TD50 hereafter) of radiocesium for the butterfly was first obtained in Nohara et al. [10] based on the power function fit for data points from relatively high-dose diets. Later, the data points from the relatively low-dose diets were added to the previous data [11]. The mathematical model fits for these combined data were performed using the power function and Weibull function models [12]; the sigmoidal data fit with the Weibull function model yielded a TD50 value of 0.45 Bq body−<sup>1</sup> (meaning that a cumulative dose of 0.45 Bq per larva results in abnormality or death in 50% of the population). A loose threshold was detected at approximately 10 mBq body−<sup>1</sup> .

The mean body weight of larvae was 0.0346 g. Therefore, the TD50 can be read as 13 kBq kg−<sup>1</sup> body weight. Here, I assume an average Japanese male person (30–49 years old) has a body weight of 68.5 kg, according to a survey by the Ministry of Health, Labour and Welfare [94]. For this average person, 13 kBq kg−<sup>1</sup> body weight is multiplied by 68.5 kg body weight, resulting in a TD50 of 890.5 kBq body−<sup>1</sup> for an average Japanese male human. This average person eats 1.555 kg diet day−<sup>1</sup> when nutritional balance is maintained [95].

Based on these data, the radioactivity concentration of diets required to reach the TD50 value in a given time span in a Japanese male human can be calculated (**Figure 3a**). To consume 890.5 kBq in 1 day, 890.5 kBq must be contained in a 1.555 kg diet; thus, the radioactivity concentration of 573 kBq kg−<sup>1</sup> diet must be consumed to reach the TD50 value in 1 day. To consume 890.5 kBq within 1 year (365 days), a 1.57 kBq kg−<sup>1</sup> diet is required. Similarly, a 157 Bq kg−<sup>1</sup> diet and a 15.7 Bq kg−<sup>1</sup> diet are required to reach the TD50 value in 10 years and 100 years, respectively. Clearly, a 15.7 Bq kg−<sup>1</sup> diet is mostly negligible for this average person between the age of 30 and 49 because he will naturally die before he reaches a 50% chance of becoming sick. However, *a 157 Bq kg−1 diet is not negligible for this average person because there is still a 50% chance of becoming sick in the next 10 years*.

Having mentioned these points, a discussion based on the TD50 value is probably as insightful as a discussion on the current political dose limits, which are based on the effective dose limits recommended by the ICRP [97]. In these conventional cases, no field effects were considered. Fortunately, based on the discussion above, the current regulation limit in Japan, i.e.,

considered as a starting point for this type of discussion. I believe that the theoretical results above are an important first step from which we can at least present the potential values for

It can be concluded that the "low-dose" exposure from the Fukushima nuclear accident imposed potentially non-negligible toxic effects on organisms including butterflies and humans through field effects. At the high-dose exposure, the same field effects would exist, but they would likely be masked by the acute damage. The direct effects may be assessed reasonably by dosimetric analysis even in the field cases, especially for high-dose cases. The field-laboratory paradox is not really a paradox; rather, it indicates our fragmentary knowl-

Although this chapter sheds light on one important low-dose issue, there are many other issues associated with the field effects that should be studied both in the field and in the laboratory. One of these issues is the *adaptive and evolutionary responses* of organisms to environmental radiation in contaminated areas. The pale grass blue butterfly appears to have evolutionarily adapted to the environmental pollutants [98]. This adaptive evolution may be largely in response to the field effects because the butterfly is essentially very resistant to direct irradiation without any possible adaptive response (unpublished data). However, the direct ionizing damage on DNA would also play an important role in adaptive response if such damage exists.

Simply because there are multiple effective pathways of the field effects, *sensitivity variations* to different modes may vary considerably among species and even among individuals in a given species. The net effects may be determined through synergistic amplification. To further understand the effects of the Fukushima pollution, multifaceted scientific approaches that are firmly based on field work and field-based laboratory experiments (such as the internal exposure experiments using the field-harvested leaves) are expected in the future. A mechanistic understanding of the indirect field effects is also necessary to advance this field of pollution biology. Simultaneously, studies on the mechanisms of the direct ionizing effects in the field (although the final effects may also be affected by the indirect field effects) should be advanced. As pointed out by Steen [99], multifaceted analyses at the DNA and genomic levels are expected to reveal evidence for direct DNA damage in the field after the Fukushima nuclear accident. I believe that the immediate early exposures to short-lived radionuclides impacted DNA directly, which then might have been inherited to subsequent generations. Such evidence would firmly establish the adverse biological effects caused by the Fukushima nuclear accident at the molecular level. Furthermore, spatiotemporal changes of such DNA damage would reveal population-level dynamics of adaptive evolution in the field, serving as an

for general foods, may not be a completely wrong value. In fact, this value can be

Understanding Low-Dose Exposure and Field Effects to Resolve the Field-Laboratory Paradox…

http://dx.doi.org/10.5772/intechopen.79870

63

100 Bq kg−<sup>1</sup>

risk assessment and management.

**10. Conclusions and future perspectives**

edge on the real-world pollution caused by this nuclear accident.

Additionally, the number of days (or years) required to reach the TD50 value when 100 Bq kg−<sup>1</sup> diet or 10 Bq kg−<sup>1</sup> diet is consumed can be calculated (**Figure 3b**). *When an average Japanese male human consumes a 100 Bq kg−1 diet*, *it takes 16.7 years to reach the TD50 value*. This is a nonnegligible time span. However, a 10 Bq kg−<sup>1</sup> diet may be negligible because it takes 167 years to reach the TD50 value, which is beyond the human lifespan.

Considering that the amount (becquerel) of radioactivity concentration of 134Cs and 137Cs discussed above is as low as the amount of naturally occurring 40K, a counter argument to this discussion would be that no harmful effect is expected from the conventional dosimetric view. However, it should be remembered that the amount of radiocesium is simply an indication of pollution levels in terms of the field effects. Moreover, we have experimental evidence that artificial radiocesium is clearly harmful at radioactivity levels as low as those observed for radiopotassium (unpublished data). I will discuss this important issue if there is an opportunity to do so in the future.

It should also be remembered that the discussion above completely ignored the dose-rate effects and the physiological differences between butterflies and humans, which include different biological half-lives and organ accumulation of cesium species. This study also ignored the different types of indirect field effects that may be species-specific, depending on the ecological status of a species. It should also be noted that *the TD50 state is toxicologically convenient to evaluate potential effects*, *but it means a devastating massive outbreak of diseases in terms of public health*. Another viewpoint to consider is that toxicological evaluations are often misleading and give the impression that anything that does not reach the TD50 value within a reasonable time or does not exceed the limit is completely safe for everybody. Scientists and politicians should pay special attention to minorities who may still be affected at this level [48, 96].

**Figure 3.** Extrapolation of toxicological data from the pale grass blue butterfly to an average Japanese male human. (a) Linearly extrapolating the butterfly data to understand the relationship between radioactivity concentration in consumed diet and time to reach TD50. For example, to reach the TD50 value in 10 years, an average daily consumption of a diet containing 157 Bq kg−<sup>1</sup> diet is required. (b) Linear relationship between cumulative radioactivity in a body and time to reach TD50. Lines with daily 100 Bq kg−<sup>1</sup> consumption and 10 Bq kg−<sup>1</sup> consumption are shown. When an average of 100 Bq diet is consumed daily, it takes 16.7 years for a Japanese male human to reach the TD50 value (8.9 × 10<sup>5</sup> Bq body−<sup>1</sup> ).

Having mentioned these points, a discussion based on the TD50 value is probably as insightful as a discussion on the current political dose limits, which are based on the effective dose limits recommended by the ICRP [97]. In these conventional cases, no field effects were considered. Fortunately, based on the discussion above, the current regulation limit in Japan, i.e., 100 Bq kg−<sup>1</sup> for general foods, may not be a completely wrong value. In fact, this value can be considered as a starting point for this type of discussion. I believe that the theoretical results above are an important first step from which we can at least present the potential values for risk assessment and management.
